Polymorphisms in lncRNA CCAT1 on the susceptibility of lung cancer in a Chinese northeast population: A case-control study.

OBJECT: To explore the association of rs1948915, rs7013433 in long noncoding RNA (lncRNA) CCAT1 and rs6983267 in MYC enhancer region with the risk of lung cancer in a Chinese northeast population, a case-control study was conducted. METHODS: The hospital-based case-control study contained 669 lung cancer patients and 697 healthy controls. Taqman® Probe allele resolution was used for genotyping. The differences between the case-control groups were analyzed using Student t-test and chi-square test. Logistic regression analysis was used to assess the relationship between the genotypes and the risk of lung cancer. Cross-generation analysis was used to explore the relationship between gene-environment interaction and lung cancer. RESULTS: There was no association between the three selected single-nucleotide polymorphisms (SNPs) and the susceptibility of lung cancer. Rs1948915 CT was correlated with lung adenocarcinoma. In female stratification, rs1948915 CT/CC was associated with a decreased susceptibility of lung cancer significantly. Additionally, the additive and multiplicative interaction models showed that there was no interaction between the three selected SNPs and smoking status in lung cancer. CONCLUSIONS: There may be an association between lung adenocarcinoma and rs1948915 polymorphism in the Chinese northeast population, while rs7013433 and rs6983267 might have no association. There was no interaction between the three selected SNPs and smoking status.

A study of performance evaluation of cobas e 801 infectious diseases panel.

BACKGROUND: Infectious diseases, such as HCV infection, HBV infection and syphilis, put a huge burden on public health. Accurate and fast testing is required for clinical usage. OBJECTIVES: This study aimed to evaluate the clinical performance of Elecsys® Anti-HCV II, Elecsys® HBsAg II and Elecsys® Syphilis using samples from routine diagnosis in China. METHODS: Specificity was tested in approximately 3000 unselected pseudonymized samples from routine clinical patients for each assay. Sensitivity of HCV and HBsAg assays was tested in 2 seroconversion panels, respectively. RESULTS: The 3 investigational assays on cobas e 801 were showed to have excellent sensitivity and specificity which is comparable to existing assays. CONCLUSION: They are suitable for routine clinical diagnostic use, including pre-operative assessment in China.

Higher Genetic Diversity and Viral Evolution in Key Regions of the Envelope Gene Are Associated with Broader Neutralizing Antibody Responses: a Report of Two Chronic HIV Infected Cases.

Dozens of broadly neutralizing antibodies (bnAbs) have been identified from chronically infected HIV-1 patients, but it is still unclear what determines the acquisition of broad neutralizing activities. Two chronic HIV-1 infected cases with similar autologous neutralizing activities were followed up for two years to study the viral evolution of the envelope gene and the neutralizing activity against autologous and heterologous viruses. The neutralization activities against homologous viruses gradually increased in both patients. HA172 eventually developed a cross-clade neutralizing antibodies response, with a neutralization breadth of 88.9% (8/9) against tier 2 heterologous HIV-1. However, HA084 could only neutralize 44.4% (4/9) of the same virus panel. Higher genetic diversity of the env gene at baseline (0.027 vs. 0.002, p ＜ 0.001), stronger immune pressure on V3 (3.08 vs. 0.99, p ＜ 0.001) or V4 loops (2.63 vs. 0.62, p = 0.002), increasing length of V1V2 and V4 loops, and evolution on V1V2 and CD4-binding sites (CD4bs) were identified in HA172. The findings demonstrated that higher viral genetic diversity, viral evolution on V1V2 and CD4bs might contribute to the development of bnAbs. The findings indicate the possibility of inducing better neutralizing antibodies in immunodeficient patients and may help develop an immune therapy strategy based on bnAbs.

V4 region of the HIV-1 envelope gene mediates immune escape and may not promote the development of broadly neutralizing antibodies.

To date, inducing the production of broadly neutralizing antibodies (bnAbs) against HIV-1 in humans has been unsuccessful. Several studies have explored the coevolution of HIV-1 and neutralizing antibodies (nAbs), but little is known about what affects the lack of bnAbs after long-term infection. A better understanding of the coevolution of the virus and nAbs in cases involving no bnAb production will help in the design of an effective HIV-1 vaccine. An individual with acute CRF01_AE HIV-1 infection who lacked bnAbs at just over 2 years post-infection (p.i.) was identified from a cohort of HIV negative men who have sex with men. The coevolution of the viral envelope gene and nAbs was studied over 741 days p.i. Strain-specific antibodies (ss-Abs) to the transmitted/founder (T/F) virus developed within 54 days p.i., but plasma collected at subsequent time points could not neutralize synchronous viruses until 557 days p.i., when the plasma acquired low-level synchronous but not heterologous neutralizing activity. The V4 region of envelope gene mutated firstly and continually evolve up to 2 years p.i. Multiple variations in the V4 region, including substitutions, deletions and glycosylation mutations, were driven by ss-Abs and mediated immune escape partially by impacting the binding of nAbs to the virus. The remarkable variations in the V4 region mediated immune escape from ss-Abs and contributed to the affinity maturation of ss-Abs against the T/F virus but may not promote the development of bnAbs. Thus, the V4 region might not be a good target for an HIV-1 vaccine.

Spatiotemporal hierarchy in antibody recognition against transmitted HIV-1 envelope glycoprotein during natural infection.

BACKGROUND: Majority of HIV-1 infection is established by one transmitted/founder virus and understanding how the neutralizing antibodies develop against this virus is critical for our rational design an HIV-1 vaccine. RESULTS: We report here antibody profiling of sequential plasma samples against transmitted/founder HIV-1 envelope glycoprotein in an epidemiologically linked transmission pair using our previously reported antigen library approach. We have decomposed the antibody recognition into three major subdomains on the envelope and showed their development in vivo followed a spatiotemporal hierarchy: starting with the ectodomain of gp41 at membrane proximal region, then the V3C3V4 and the V1V2 of gp120 at the membrane distal region. While antibodies to these subdomains appeared to undergo avidity maturation, the early anti-gp41 antibodies failed to translate into detectable autologous neutralization. Instead, it was the much delayed anti-V3C3V4 and anti-V1V2 antibodies constituted the major neutralizing activities. CONCLUSIONS: Our results indicate that the initial antibody response was severely misguided by the transmitted/founder virus and future vaccine design would need to avoid the ectodomain of gp41 and focus on the neutralizing targets in the V3C3V4 and V1V2 subdomains of gp120.

Immunological and virological benefits resulted from short-course treatment during primary HIV infection: a meta-analysis.

OBJECTIVES: To assess the potential immunological and virological effects that result from short-course antiretroviral treatment during primary HIV infection (PHI). And to investigate whether treatment initiation time, treatment duration and follow-up time after treatment interruption would affect these post-treatment immunovirological outcomes. METHODS: We systematically searched PubMed, Cochrane Library (to September 2013) and retrieved conference abstracts for studies regarding effects of early treatment during PHI on CD4 count and viral load (VL). Using the method of calculating weighted mean differences with Stata11.0, we conducted meta-analyses on the effect of early treatment on CD4 count and VL. Then we performed subgroup analyses by follow-up time after treatment interruption, treatment initiation time and treatment duration. Baseline immunovirological characteristics were also analyzed to account for potential bias. RESULTS: Compared to the untreated arm, treatment during PHI not only increased CD4 count by 85.92 cells/µl but also lowered viral load by 0.30 log copies/ml within one year after treatment interruption. However, the benefits declined gradually, reaching no significance 12-24 months after treatment interruption. Baseline immunovirological characteristics and sensitivity analyses of randomized controlled trials indicated that the benefits mentioned above were underestimated. Extending treatment duration beyond 12 months did not increase efficacy. CONCLUSIONS: Short-course treatment during PHI was associated with immunological and virological benefits which last for at least one year after treatment interruption. The conclusions from our study would help the decision-making in the clinical management of PHI.

[Association between amino acid mutations in Gag protein and human leukocyte antigen class I alleles in human immunodeficiency virus-1 B' infected Han Chinese people].

OBJECTIVE: To explore the human leukocyte antigen (HLA)-associated mutations in Gag protein of B' clade (human immunodeficiency virus-1) HIV-1 infected Han Chinese people and evaluate the impact of HLA associated Gag mutations on the disease progression of HIV infection. METHODS: A total of 95 B' clade HIV-1 infected Han Chinese cases were recruited. The gag sequences were amplified from viral RNA and sequenced directly. HLA-I genotypes were detected with the assay of polymerase chain reaction-sequence specific primer (PCR-SSP). HLA-associated mutations were identified and the relationships between HLA-associated mutations and CD4+ T cell counts or plasma viral loads analyzed. RESULTS: Forty-seven kinds of mutations at 28 sites (15, 18, 26, 30, 34, 46, 62, 67, 81, 84, 90, 102, 118, 121, 122, 125, 146, 147, 173, 176, 252, 357, 374, 376, 437, 470, 471, 478) of Gag protein were significantly associated with particular HLA class I allelotypes (P < 0.05). Among which, 9 sites (26, 30, 81, 84, 125, 146, 147, 357, 437) were located within 13 known cytotoxic T-lymphocyte (CTL) epitopes or flanking regions. The number of HLA-associated mutations was significantly associated with both CD4 T cell counts (r = -0.318, P = 0.002) and viral loads (r = 0.360, P = 0.003). CONCLUSION: HLA-associated mutations may have a significant impact on HIV disease progression in B' clade HIV-1 infected Han Chinese population.

Screening acute HIV infections among Chinese men who have sex with men from voluntary counseling & testing centers.

BACKGROUND: Recent studies have shown the public health importance of identifying acute HIV infection (AHI) in the men who have sex with men (MSM) of China, which has a much higher risk of HIV transmission. However, cost-utility analyses to guide policy around AHI screening are lacking. METHODOLOGY/PRINCIPAL FINDINGS: An open prospective cohort was recruited among MSM living in Liaoning Province, Northeast China. Blood samples and epidemiological information were collected every 10 weeks. Third-generation ELISA and rapid test were used for HIV antibody screening, western blot assay (WB) served for assay validation. Antibody negative specimens were tested with 24 mini-pool nucleic acid amplification testing (NAAT). Specimens with positive ELISA but negative or indeterminate WB results were tested with NAAT individually without mixing. A cost-utility analysis of NAAT screening was assessed. Among the 5,344 follow-up visits of 1,765 MSM in 22 months, HIV antibody tests detected 114 HIV chronic infections, 24 seroconverters and 21 antibody indeterminate cases. 29 acute HIV infections were detected with NAAT from 21 antibody indeterminate and 1,606 antibody negative cases. The HIV-1 prevalence and incidence density were 6.6% (95% CI: 5.5-7.9) and 7.1 (95% CI: 5.4-9.2)/100 person-years, respectively. With pooled NAAT and individual NAAT strategy, the cost of an HIV transmission averted was $1,480. The addition of NAAT after HIV antibody tests had a cost-utility ratio of $3,366 per gained quality-adjusted life year (QALY). The input-output ratio of NAAT was about 1∶16.9. CONCLUSIONS/SIGNIFICANCE: The HIV infections among MSM continue to rise at alarming rates. Despite the rising cost, adding pooled NAAT to the HIV antibody screening significantly increases the identification of acute HIV infections in MSM. Early treatment and target-oriented publicity and education programs can be strengthened to decrease the risk of HIV transmission and to save medical resources in the long run.